There has been a growing interest in hydroxytyrosol (HT) due to its powerful antioxidant and free-radical scavenging properties when added to formulations such as pharmaceuticals and cosmetics. To study the stability and transdermal properties of hydrogels and creams (HT-based formulations), a high-performance liquid chromatography method was developed for determining HT. In the Franz diffusion cell system, both hydrogel and cream show a rapid and similar penetration profile through the Bama miniature pig skin. However, the Strat-M® membrane exhibits slightly lower permeability and is selective to different formulations; that is, the cream has a permeability value of 10.69%, while the hydrogel has a value of 5.27%. The dynamics parameters from the permeation assays indicate that the model using the Strat-M® membrane can be used as a screening tool to evaluate the skin uptake and permeation efficacy of different formulations. Adding 3-O-ethyl-L-ascorbic acid to HT-based formulations can effectively prevent discoloration under prolonged high-temperature storage, while combining multiple antioxidants delays degradation most effectively. This study provides novel ideas for functional formulation optimization to enhance the realism and reproducibility of cosmetic products containing HT and provides scientific evidence for the production, packaging, shelf life, storage, and transportation of products.
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